The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.

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SummaryEfforts to control malaria have been boosted in the past few years with increased international funding and greater political commitment. Consequently, the reported malaria burden is being reduced in a number of countries throughout the world, including in some countries in tropical Africa where the burden of malaria is greatest. These achievements have raised new hopes of eradicating malaria. This paper summarizes the outcomes of a World Health Organization's expert meeting on the feasibility of such a goal. Given the hindsight and experience of the Global Malaria Eradication Programme of the 1950s and 1960s, and current knowledge of the effectiveness of antimalarial tools and interventions, it would be feasible to effectively control malaria in all parts of the world and greatly reduce the enormous morbidity and mortality of malaria. It would also be entirely feasible to eliminate malaria from countries and regions where the intensity of transmission is low to moderate, and where health systems are strong. Elimination of malaria requires a re-orientation of control activity, moving away from a population-based coverage of interventions, to one based on a programme of effective surveillance and response. Sustained efforts will be required to prevent the resurgence of malaria from where it is eliminated. Eliminating malaria from countries where the intensity of transmission is high and stable such as in tropical Africa will require more potent tools and stronger health systems than are available today. When such countries have effectively reduced the burden of malaria, the achievements will need to be consolidated before a programme re-orientation towards malaria elimination is contemplated. Malaria control and elimination are under the constant threat of the parasite and vector mosquito developing resistance to medicines and insecticides, which are the cornerstones of current antimalarial interventions. The prospects of malaria eradication, therefore, rest heavily on the outcomes of research and development for new and improved tools. Malaria control and elimination are complementary objectives in the global fight against malaria.

The production of histidine-rich protein II (HRP2), a histidine-and alanine-rich protein produced by Plasmodium falciparum, is closely associated with the development and proliferation of the parasite and therefore is perfectly suited to reflect growth inhibition as a measure of drug susceptibility. It was the aim of the present study to develop a malaria drug sensitivity assay based on the measurement of HRP2 in a simple enzyme-linked immunosorbent assay (ELISA). The new test proved to be as reliable as traditional in vitro assays, while it was considerably easier to establish and perform. Parasites are incubated at an initial level of parasitemia of 0.01 to 0.1% on microculture plates predosed with ascending concentrations of antimalarial drugs. After incubation for 48 to 72 h, the samples are freeze-thawed and transferred to ELISA plates. The complete ELISA takes about 2.5 h to perform, may be carried out with commercially available test kits, and requires relatively little technical equipment. In correlation analysis, the results closely paralleled those obtained by the isotopic assay (R ‫؍‬ 0.892; P < 0.0001) and World Health Organization schizont maturation tests (R ‫؍‬ 0.959; P < 0.0001). The novel HRP2 drug susceptibility assay proved to be very sensitive, simple to establish, and highly reproducible. It can be used for a wide range of applications, from epidemiological studies to the screening of new drugs, and may have the potential to replace traditional in vitro techniques. Standard operating procedures, updated information, and analytical software are available from http://malaria.farch.net.Antimalarial drug resistance has become an issue of utmost importance for the control of falciparum malaria worldwide. Individual treatment regimens as well as malaria control strategies therefore need to be based on profound knowledge of drug sensitivity. There are basically two approaches to the assessment of the antimalarial drug susceptibility of Plasmodium falciparum: in vivo and in vitro assays. The most commonly used in vitro assays, the isotopic assay, the World Health Organization (WHO) microtest, and a number of parasite lactate dehydrogenase-based assays, have their advantages but also have a number of known drawbacks (1,7,8,12,14,24,26). It was the aim of this study to develop an in vitro assay that is easy to establish and to standardize, that has a high sensitivity, and that requires little technical equipment, similar to the WHO test, but that is also as reproducible and that can be performed as fast as the isotopic assay.Histidine-rich protein II (HRP2) is a naturally occurring histidine-and alanine-rich protein localized in several cell compartments including the cytoplasm of P. falciparum. Recent studies have implicated HRP2 as an important factor in the detoxification of heme (11,16,17,21). HRP2 was identified in all P. falciparum strains regardless of knob phenotype and was recovered from plasma and culture supernatants as a secreted water-soluble protein (20). It is found as concentrated pack...

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In many areas of tropical Africa affected by chloroquine-resistant Plasmodium falciparum, a combination of sulfadoxine and pyrimethamine (S-P) is used for alternative medication, especially in young children. In Magoda village in Muheza District, north-eastern Tanzania, 38 children 1-10 years of age were enrolled in a therapeutic study of S-P in July 1994. All had monoinfections of P. falciparum and an asexual parasite count of 1000-80,000/microL of blood. S-P was given as a single dose corresponding to 0.8-1.4 mg pyrimethamine/kg body weight. Of the 38 children followed up to day 7, 10 showed an S/RI response, 26 an RII response, and 2 an RIII response. Older children had lower pre-treatment parasitaemia and a better therapeutic response than younger children. Among the various contributory factors responsible for the poor therapeutic result, drug pressure from a prophylactic intervention with weekly dapsone-pyrimethamine between May 1993 and May 1994 seems to have been the most important.